E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Low testosterone levels in men |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021012 |
E.1.2 | Term | Hypogonadotrophic hypogonadism |
E.1.2 | System Organ Class | 100000004860 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of testosterone replacement therapy in men with OPIAD on body composition, the haemostatic system, glucose metabolism, muscle function, pain sensitivity, pain modulation, lipids, sexual function and quality of life.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male patients aged 18-59 years
Treatment with opioid for >3 month, daily dose > 50-100 mg (for conversion see Annex 1)
Total testosterone < 10 nmol/l
FSH/LH levels normal or below normal laboratory values.
Normal Prolactin levels
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E.4 | Principal exclusion criteria |
Hematocrit > 54 % at screening
PSA > 3 ng/ml.
Routine blood sample values above range (TSH, ionized calcium, hemoglobin, liver- and kidney function tests)
Severe organic or mental disease reasonably suspected from history and/or clinical examination
Past or present breast or prostate cancer
Past or present liver tumors or acute or chronic hepatic diseases
Any current diagnosis of cancers
Acute thrombotic or embolic diseases
Previous VTE and Cerebrovascular disease
Uncontrolled hypertension (SBP>160mmHg and/or DBP>100mmHg) despite adequate antihypertensive therapy
Chronic debilitating disease (kidney failure, cirrhosis, HIV, COPD, heart failure or ischemic heart disease).
Epilepsy or migraine not adequately controlled by therapy.
Severe benign prostatic hypertrophy with IPSS symptom score above 19 (annex 2)
Sleep apnea
Any indication of drugs and/or alcohol abuse (>50 g alcohol a day)
Implantation of a sustained-action sex hormone in the last 12 months
Use of oral, buccal or transdermal testosterone therapy in the last 2 weeks before the first study medication, or intramuscular testosterone ester other than TU in the last 6 week, or TU injection in the last 6 months or use of androgens during the entire study period (except the study medication)
Blood coagulation irregularities presenting an increased risk of bleeding after intramuscular injection
Treatment with glucocorticoids >5mg/day and 5 alfa reductase inhibitors.
Hypersensitivity to Nebido
BMI>40 kg/m2 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint:
• Lean body mass
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
• Haemostatic status
• Pulse pressure
• 24 h blood pressure
• Lipid profile
• Waist
• Body fat
• Glucose tolerance (OGTT)
• HOMA- IR
• Liver fat content
• ACTH test
• Serum testosterone
• Bone mineral density
• Bone structure
• Physical and muscle strength tests
• Pain threshold and tolerance tests
• Sexual function
• Quality of life
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |